PROJECT SUMMARY: The goal of the Cancer Genetics and Epigenetics (CGE) Program is to better understand the fundamental mechanisms underlying genetic and epigenetic instability and its contribution to the initiation and progression of human tumors. In pursuit of this goal, the program organizes its research efforts into three areas of focus: 1) DNA damage and repair and genome instability; 2) epigenetics and gene regulation; and 3) cancer genetics /genomics. The CGE Program consists of 29 core members from 13 academic departments and three schools across Emory University, including the School of Medicine, the School of Public Health and Emory College. CGE Program members currently have $15,110,592 in research grant funding (annual direct costs), of which $12,849,105 is peer-reviewed and $4,277,290 (34%) is NCI-funded. Program members have published 227 cancer-related publications in the cun-ent project period. Among these, 12% and 25% represent intra- and inter-programmafic and interactions, respectively. In the current project period, discovery efforts have led to the identification of key genes whose mutation or altered expression contribute to cancer initiation and progression. Basic discoveries in the area of cancer epigenetics have prompted early small molecule screening efforts to identify novel targeted agents. Program development and key recruitments have strengthened and enhanced intra-programmatic activities in the areas of human radiation carcinogenesis, DNA damage/repair, and cancer genomics. This has been leveraged into several new multi-investigator grants and has provided key translational avenues for the program through increased inter-programmatic activities and cross-cutting genomics initiatives. Successful genomic studies resulted in the molecular classification of tumors and the identification of genes, gene signatures, and clinical factors with prognostic value in prostate, breast, brain, and lung malignancies. The Cancer Genetics and Epigenetics Program facilitates scientific collaborations and cancer research discoveries and has positioned itself for continued development in the forthcoming project period.